The objectives of the proposed research are to investigate the mechanisms involved in the regulation of intestinal cell proliferation. The responses of the intestinal mucosa to resection and irradiation will be analyzed using the tritium content of a known weight of intestine and a selected number of crypts at various times after injection of tritiated tymidine, as measures of the labelling index, crypt population and turnover time of intestinal epithelium. The labelled mitoses curves will be determined from autoradiographs and used to estimate the G1, G2, S, and M portions of the cell generation time. Having defined those situations in which reproducible changes in kinetic parameters can be induced, the technique of parabiosis will be employed in attempts to determine whether humoral factors are involved in the compensatory response of the intestinal mucosa following resection or irradiation. Using the methods employed in single animals, the kinetics of the intestinal epithelium will be analyzed in both resected and non-resected, irradiated and unirradiated rats joined in parabiotic union. If it is possible to implicate humoral factors in the control of cell proliferation and migration, then attempts will be made utilizing techniques of protein separation, to purify such substances and determine their chemical properties. The objective would then be to use these substances to obtain antisera which could be suitably labelled and reinjected in attempts to elucidate sites of production and possible modes of action.